Until recently, it has been necessary to rely on difficult-to-perform studies of small, spatially homogeneous areas of myocardial tissue using microelectrodes to provide much of our understanding of basic electrophysiological and pharmacological mechanisms in myyocardium. These studies, however, are unable to produce time-dependent mappings of the spread of electrical excitation over larger areas of heart tissue. Such mappings are necessary for understanding not only the normal propagation routes of the cardiac action potential but also the alterations in these pathways that can lead to cardiac arrhythmias. Recently developed probes for optical monitoring of electrical activity in cardiac tissue, however, have now made it possible to visualize the two-dimensional wavefronts of the action potential, and to thereby map its spread. These probes use voltage-sensitive dyes that change their optical properties in response to transmembrane potential changes. It is the overall objective of the proposed work to use optical monitoring of electrical activity to determine the role of spatial interactions between pacemaker and follower cell regions in the generation of supraventricular arrhythmias and how such interactions are modified by naturally occurring and therapeutically administered agents. Specifically, we will use rabbit sinoatrial tissue to study the effects of autonomic neurotransmitters, ouabain, and antiarrhythmic drugs on pacemaker location and patterns of electrical propagation. We will lso study the effect of variations in the refractory period in different regions of the sinoatrial node in contributing to generation of reentrant arrhythmias. A fundamental question which we hope to answer is: are supraventricular arrhythmias due to irregular activity at a specific site or are they due to disruption of the normal spatial interactions between the pacemaker region and the follower cell regions?